We are developing Raman spectroscopy for in vivo diagnosis of atherosclerosis. A clinically usable diagnostic system which includes a diode laser operating at 830 nm, holographic tranmissive grating-based spectrograph with F#2 collection optics, a notch filter for rejection of Rayleigh scattered light, an AR coated deep depletion (CCD) detector for high sensitive detection has been assembled. Fiber optic probes (with integrated dielectric filters at the distal tip to reduce fluorescence/Raman background signal) to be used in catheter based in vivo studies are currently undergoing a design, refinement and testing process to allow clinically acceptable data acquisition. Once the performance of the system is evaluated clinical studies will begin at the Cleveland Clin Fdn, Cleveland, MetroWest Medical Center, Boston, and Leiden University Hospital, The Netherlands. Detailed studies of various disease states and their progression will eventually allow for optimal preventative measures and assessment of treatment protocol efficacy.